iGAS Disease Research Articles

Attribution of invasive group A streptococcal infections (iGAS) to predisposing viral infections, the Netherlands, 2010 to 2023.

BackgroundAfter most COVID-19 pandemic control measures were lifted in 2022, many infectious diseases re-emerged. An increase in invasive group A streptococcal (iGAS) infections among adults and young children was reported by several countries. Viral infections including influenza and varicella, known risk factors for iGAS infection, also increased.AimTo estimate the proportion of GAS skin and soft tissue infections (SSTI) and pneumonia/sepsis in children (≤ 5 years) attributable to varicella, and the proportion of GAS pneumonia/sepsis in children and adults attributable to potentially predisposing respiratory viruses influenza A and B, RSV, hMPV and SARS-CoV-2 in the Netherlands.MethodsWe performed time series regression using weekly data on respiratory viruses, varicella and non-invasive GAS infections and GAS isolates cultured from blood, lower airways, skin, pus and wounds, from January 2010 to March 2023.ResultsIn 2010-19, 50% (95% CI: 36-64) of GAS SSTI in children were attributable to varicella. Between January 2022 and March 2023, 34% (95% CI: 24-43) of GAS SSTI cases were attributable to varicella. Of iGAS pneumonia/sepsis between January 2022 and March 2023, 34% (95% CI: 20-49) and 25% (95% CI: 18-32) was attributable to respiratory virus infections in children and adults, respectively, with the largest contributor (17%) being influenza A.ConclusionsPredisposing viral infections likely contributed to, but cannot fully explain, the observed iGAS increase among children and adults in 2022-23 in the Netherlands. Public health measures to control viral infections, such as vaccination against varicella or influenza, might reduce the iGAS disease burden.

Are Invasive Group A Streptococcal Infections Preventable by Antibiotic Therapy?: A Collaborative Retrospective Study.

In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a simultaneous increase in consultations for scarlet fever and pharyngitis was reported in England, leading to the recommendation to treat any suspected GAS disease with antibiotics, guidelines in Germany and Switzerland remained unchanged. We aimed to investigate whether this policy was appropriate. We conducted a retrospective multicenter study of children hospitalized for invasive GAS disease between September 2022 and March 2023 in pediatric departments in Dresden and Berlin (Germany) and Basel (Switzerland). We reviewed medical records and conducted structured telephone interviews to analyze whether suspected GAS infections with or without antibiotic treatment were reported prehospitalization. In total, 63 patients met the inclusion criteria (median age 4.2 years, 57% males); however, clinical information was not complete for all analyzed characteristics; 32/54 (59%) had ≥1 physician visit ≤4 weeks prehospitalization. In 4/32 (13%) patients, GAS disease, that is, tonsillitis or scarlet fever, was suspected; 2/4 of them received antibiotics, and a positive rapid antigen test for GAS was documented in 1 of them. A small minority of patients had suspected GAS infection within 4 weeks before iGAS disease. These data suggest that there is little opportunity to prevent iGAS disease by antibiotic therapy, because in most patients-even if seen by a physician-there was either no evidence of GAS disease or when GAS disease was suspected and treated with antibiotics, consecutive invasive GAS disease was not prevented.

Chains of misery: surging invasive group A streptococcal disease.

We describe the epidemiology of the recent global surge in invasive group A streptococcal (GAS) disease and consider its proximate and distal causes. We highlight important knowledge gaps regarding clinical management and discuss potential strategies for prevention. Rates of invasive GAS (iGAS) disease were increasing globally prior to the COVID-19 pandemic. Since mid-2022, following the worst years of the pandemic in 2020 and 2021, many countries with systems to monitor GAS syndromes have reported surges in cases of iGAS concurrent with increased scarlet fever, pharyngitis, and viral co-infections. The emergence of the hypervirulent M1UK strain as a cause of iGAS, particularly in high income countries, is concerning. New data are emerging on the transmission dynamics of GAS. GAS remains universally susceptible to penicillin but there are increasing reports of macrolide and lincosamide resistance, particularly in invasive isolates, with uncertain clinical consequences. Intravenous immunoglobulin is used widely for streptococcal toxic shock syndrome and necrotizing soft tissue infections, although there is limited clinical evidence, and none from a completed randomized controlled trial. Intensive and expensive efforts at population-level control of GAS infections and postinfectious autoimmune complications have been only partially successful. The great hope for control of GAS diseases remains vaccine development. However, all modern vaccine candidates remain in the early development stage. In many countries, iGAS rates surged from mid-2022 in the aftermath of pandemic control measures and physical distancing. The emergence of a dominant hypervirulent strain is an important but incomplete explanation for this phenomenon. Clinical management of iGAS remains highly empirical and new data has not emerged. A vaccine remains the most likely means of achieving a sustainable reduction in the burden of iGAS.

Invasive group A Streptococcus infection (Streptococcus pyogenes): Current situation in Spain.

Group A ß-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic.

Invasive group A streptococcal disease surveillance in Canada, 2021-2022.

Invasive group A streptococcal (iGAS, Streptococcus pyogenes) disease has been a nationally notifiable disease in Canada since 2000. This report summarizes the demographics, emm types, and antimicrobial resistance of iGAS isolates collected in Canada in 2021 and 2022. The Public Health Agency of Canada's National Microbiology Laboratory collaborates with provincial and territorial public health laboratories to conduct national surveillance of invasive S. pyogenes. Emm typing was performed using the Centers for Disease Control and Prevention emm sequencing protocol or extracted from whole-genome sequencing data. Antimicrobial susceptibilities were determined using Kirby-Bauer disk diffusion according to Clinical and Laboratory Standards Institute guidelines or predicted from whole-genome sequencing data based on the presence of resistance determinants. Overall, the incidence of iGAS disease in Canada was 5.56 cases per 100,000 population in 2021, decreasing from the peak of 8.6 cases per 100,000 population in 2018. A total of 2,630 iGAS isolates were collected during 2022, representing an increase from 2021 (n=2,179). In particular, there was a large increase in isolates collected from October to December 2022. The most predominant emm type overall in 2021 and 2022 was emm49, at 21.5% (n=468) and 16.9% (n=444), respectively, representing a significant increase in prevalence since 2018 (p<0.0001). The former most prevalent type, emm1, increased from 0.5% (n=10) in 2021 to 4.8% (n=125) in 2022; similarly, emm12 increased from 1.0% (n=22) in 2021 to 5.8% (n=151) in 2022. These two types together accounted for almost 25% of isolates collected in late 2022 (October to December). Antimicrobial resistance rates in 2021 and 2022 included: 14.9%/14.1% erythromycin resistance, 4.8%/3.0% clindamycin resistance, and <1% chloramphenicol resistance. The increase of iGAS isolates collected in Canada is an important public health concern. Continued surveillance of iGAS is critical to monitor expanding emm types and antimicrobial resistance patterns.

M1UKStreptococcus pyogenes causing community-acquired pneumonia, pleural empyema and streptococcal toxic shock syndrome

Streptococcus pyogenes causes superficial infections but can also cause deep-seated infections and toxin-mediated diseases. In the present study, phylogenetic and in silico prediction analyses were performed on an antimicrobial resistant M1UKS. pyogenes strain causing severe clinical manifestations during the current surge of invasive group A Streptococcus (iGAS) disease. A 40-year-old patient was admitted to the hospital with fever, chest pain and fatigue. Based on the clinical and laboratory findings, a diagnosis of sepsis with disseminated intravascular coagulation, community-acquired pneumonia, pleural empyema and streptococcal toxic shock syndrome was made. Microbial identification was performed by multiplex PCR and conventional culturing. Furthermore, antimicrobial susceptibility testing, whole genome sequencing, phylogenomic analysis and in silico prediction analysis of antimicrobial resistance genes and virulence factors were performed. S. pyogenes isolates were detected in pleural fluid and sputum of the patient. Both isolates belonged to the M1UK lineage of the emm1/ST28 clone, being closely related with an M1UK GAS strain from Australia. They exhibited resistance to erythromycin and clindamycin and susceptibility-increased exposure to levofloxacin and carried genes encoding for protein homologues of antibiotic efflux pumps. Moreover, several virulence factors, and a previously described single-nucleotide polymorphism in the 5' transcriptional leader sequence of the ssrA gene, which enhances expression of SpeA, were detected. The present antimicrobial-resistant M1UKS. pyogenes strain represents the first report of this emerging lineage associated with such manifestations of iGAS disease.

Invasive group A streptococcal infections in children and adolescents in Denmark during 2022–23 compared with 2016–17 to 2021–22: a nationwide, multicentre, population-based cohort study

A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22). In this nationwide, multicentre, population-based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's χ2 test. Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 22·6 (95% CI 14·7-33·1) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 66·0 (52·0-82·6) per 1 000 000 during 2023-23 (RR 2·9, 95% CI 1·9-4·6; p<0·0001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 6·1 (95% CI 2·4-12·5) per 1 000 000 children and adolescents. In 2022-23, there was a 9·5-fold increase in emm-12 (95% CI 2·2-40·8; p=0·0002) and a 2·7-fold increase in emm-1 (1·3-5·5; p=0·0037). The most common clinical manifestations of iGAS in 2022-23 were soft-tissue infections, which increased by 4·5-fold (1·9-10·9; p=0·0003), and complicated pneumonia with parapneumonic effusion, which increased by 4·0-fold (1·4-11·4; p=0·0059), both compared with the three pre-COVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=0·39), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=0·53), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=0·84), or mortality (three [4%] of 76 vs three [3%] of 98; p=1·00). In 2022-23, there was a 3·6-fold (95% CI 1·8-7·3; p=0·0001) increase in children with a preceding upper respiratory tract infection and a 4·6-fold (1·5-14·1; p=0·0034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons. In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three pre-COVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents. Innovation Fund Denmark.

98. Resurgence of Invasive Group A Streptococcal Disease in Utah Children

Abstract Background Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections in childhood as well as life-threatening invasive infections. Since 1997, emm1 has been the most common emm type associated with invasive GAS (iGAS) in the US. Apparent increases in iGAS have been reported in several countries during the winter of 2022-23. We sought to characterize changing clinical and molecular epidemiology of iGAS disease in Utah children before and after the emergence of COVID-19. Methods We retrospectively identified children 0-18 years with iGAS treated at Primary Children’s Hospital (Salt Lake City, Utah) from 2018- 2023. Cases were identified through the laboratory database. Electronic health record review confirmed that cases met the CDC definition of iGAS and streptococcal toxic shock syndrome (STSS). We abstracted demographics, disease classification and outcomes (Table). Comparisons were made across years. GAS isolates underwent whole genome sequencing for emm type determination. Results From 1/2018 to 3/2023, we identified 141 cases of iGAS. Case numbers ranged from 6/yr (2021) to 39 (2019). The highest number of cases by quarter was seen in Q1 2023 (Figure). We observed a marked decrease in iGAS from Q1 2020 through Q3 2022 followed by a steep increase, coinciding with surges in RSV and influenza. Demographics were similar across the study period. 60% of iGAS cases were in males. Complicated pneumonia and head/neck infections predominated. iGAS associated with STSS appeared higher post-pandemic (4/73 [5%] cases in 2018-19 vs. 8/51 [16%] in 2022-23 [OR = 3.2; 95% CI 0.8-15]). The majority of STSS (7/12; 57%) was associated with complicated pneumonia. Clinical outcomes were comparable pre- and post-pandemic. emm types were available for 49/51 (96%) of isolates in 2022-23. emm1 and emm12 were associated with 67% of iGAS disease (emm1 n = 16 [33%]; emm12 n = 17 [35%]). Conclusion After a marked drop in iGAS infections in children during the COVID-19 pandemic in Utah there was a resurgence of iGAS starting in late 2022 and early 2023, modestly exceeding pre-pandemic levels. emm1 and emm12 predominated in the surge. Further analysis of disease severity and molecular epidemiology are in progress. Disclosures Kwabena Krow Ampofo, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support Andrew T. Pavia, MD, GlaxoSmith Kline: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics: Grant/Research Support|BioFire Diagnostics: I have IP owned by the U. of Utah licensed to BioFire and receive royalties. I have been a consultant and received grant support as well.|Merck and Company, Inc.: Advisor/Consultant

Group A Streptococcus Infection in Neonatal Population: A Systematic Review of The Literature.

(1) Background: The importance of group A streptococcus (GAS) infection severity has been recognized in children and adults. However, to our knowledge, there have been no systematic reviews or pooled assessments of the incidence and outcome of invasive GAS (iGAS) disease in neonates, a potentially high-risk population. Therefore, we performed a systematic review of available data regarding the risk factors, clinical presentation, and outcome of GAS infection in neonates. (2) Methods: An electronic search of the existing literature was carried out during the period July 2023-September 2023 in the PubMed and Scopus databases, considering studies referring to GAS infection in the neonatal population. (3) Results: Overall, 39 studies met all the inclusion criteria and were included in this review, evaluating data from 194 neonates. Unfortunately, there were a lot of missing data among the retrieved studies. Our systematic review highlighted the presence of differences with regards to clinical presentation, infection sites, and outcome of GAS invasive disease between neonates with early-onset (EOS) or late-onset sepsis (LOS). Common characteristics of EOS included respiratory distress, rapid deterioration, and high mortality rate irrespective of the infection site, while rash, gastrointestinal tract symptoms, and fever appeared to be the most frequent symptoms/clinical signs and manifestations of LOS disease. The management of severe invasive iGAS disease consists mainly of specific antimicrobial treatment as well as supportive care with fluids and electrolyte supplementation, minimizing or counteracting the effects of toxins. Furthermore, a mortality rate of approximately 14% was recorded for iGAS disease in the total of all studies' neonates. (4) Conclusions: Although iGAS is a rare entity of neonatal infections, the potential severity of the disease and the rapid deterioration requires the development of quick analysis methods for the detection of GAS allowing the prompt diagnosis and administration of the indicated antibiotic treatment. Furthermore, given the exceptional risk for both the pregnant woman and the neonate, it is very important to raise awareness and create easily accessible guidelines that could facilitate the prevention and management of maternal as well as the subsequent neonatal severe iGAS disease.

Influenza enhances host susceptibility to non-pulmonary invasive Streptococcus pyogenes infections

ABSTRACT Streptococcus pyogenes (group A streptococcus; GAS) causes a variety of invasive diseases (iGAS) such as bacteremia, toxic shock syndrome, and pneumonia, which are associated with high mortality despite the susceptibility of the bacteria to penicillin ex vivo. Epidemiologic studies indicate that respiratory influenza virus infection is associated with an increase in the frequency of iGAS diseases, including those not directly involving the lung. We modified a murine model of influenza A (IAV)-GAS superinfection to determine if viral pneumonia increased the susceptibility of mice subsequently infected with GAS in the peritoneum. The results showed that respiratory IAV infection increased the morbidity (weight loss) of mice infected intraperitoneally (i.p.) with GAS 3, 5, and 10 d after the initial viral infection. Mortality was also significantly increased when mice were infected with GAS 3 and 5 d after pulmonary IAV infection. Increased mortality among mice infected with virus 5 d prior to bacterial infection correlated with increased dissemination of GAS from the peritoneum to the blood, spleen, and lungs. The interval was also associated with a significant increase in the pro-inflammatory cytokines IFN-γ, IL-12, TNF-α, MCP-1 and IL-27 in sera. We conclude, using a murine model, that respiratory influenza virus infection increases the likelihood and severity of systemic iGAS disease, even when GAS infection does not originate in the respiratory tract.

Prevalence of erythromycin-resistant emm92-type invasive group A streptococcal infections among injection drug users in West Virginia, United States, 2021-23.

Increasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and the USA over the past several years. Coupled with this are observations of higher rates of resistance to erythromycin and clindamycin. To characterize iGAS and pharyngitis isolates from West Virginia (WV), a US state outside of the national Active Bacteria Core surveillance purview, where risk factors associated with iGAS infections are prevalent. Seventy-seven invasive group A Streptococcus isolates were collected from 67 unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021 to 2023. Invasive isolates and 20 unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibility in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm subtype and detection of MLSB resistance determinants. Twenty-six (39%) isolates were of a single emm92 type. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported IV drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, 51 (76%) of the 67 iGAS isolates were determined to carry MLSB resistance. Isolates of emm92 type (clonal subtype emm92.0) were associated with iGAS infections in adult IV drug users, but not with paediatric pharyngitis, and were uniformly resistant to erythromycin and clindamycin.

Increase in invasive group A streptococcal disease among Australian children coinciding with northern hemisphere surges

Increases in invasive group A streptococcal disease (iGAS) have recently been reported in multiple countries in the northern hemisphere, occurring during, and outside of, typical spring peaks. We report the epidemiology of iGAS among children in Australia from 1 July 2018 to 31 December2022. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network prospectively collected iGAS patient notifications for children and young people aged less than 18 years admitted to five major Australian paediatric hospitals in Victoria, Queensland, Western Australia and the Northern Territory. Patients were eligible for inclusion if they had GAS isolated from a normally sterile body site, or met clinical criteria for streptococcal toxic shock syndrome or necrotising fasciitis with GAS isolated from a non-sterile site. We report patients' clinical and demographic characteristics, and estimate minimum incidence rates. We identified 280 paediatric iGAS patients, median age 4.5 years (interquartile range 1.4-6.4). We observed a pre-pandemic peak annualised incidence of 3.7 per 100,000 (95% CI 3.1-4.4) in the 3rd quarter of 2018, followed by a decline to less than 1.0 per 100,000 per quarter from 2020 to mid-2021. The annualised incidence increased sharply from mid-2022, peaking at 5.2 per 100,000 (95% CI 4.4-6.0) in the 3rd quarter and persisting into the 4th quarter (4.9 per 100,000, 95% CI 4.2-5.7). There were 3 attributable deaths and 84 (32%) patients had severe disease (overall case fatality rate 1%, 95% CI 0.2-3.3). Respiratory virus co-infection, positive in 57 of 119 patients tested, was associated with severe disease (RR 1.9, 95% CI 1.2-3.0). The most common emm-type was emm-1 (60 of 163 isolates that underwent emm-typing, 37%), followed by emm-12 (18%). Australia experienced an increase in the incidence of iGAS among children and young people in 2022 compared to pandemic years 2020-2021. This is similar to northern hemisphere observations, despite differences in seasons and circulating respiratory viruses. Outbreaks of iGAS continue to occur widely. This emphasises the unmet need for a vaccine to prevent significant morbidity associated with iGAS disease. Murdoch Children's Research Institute funded open access publishing of this manuscript.

Novel emm4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022.

Invasive group A streptococcal (iGAS) disease cases increased in the first half of 2022 in the Netherlands, with a remarkably high proportion of emm4 isolates. Whole-genome sequence analysis of 66 emm4 isolates, 40 isolates from the pre-coronavirus disease 2019 (COVID-19) pandemic period 2009-2019 and 26 contemporary isolates from 2022, identified a novel Streptococcus pyogenes lineage (M4NL22), which accounted for 85 % of emm4 iGAS cases in 2022. Surprisingly, we detected few isolates of the emm4 hypervirulent clone, which has replaced nearly all other emm4 in the USA and the UK. M4NL22 displayed genetic differences compared to other emm4 strains, although these were of unclear biological significance. In publicly available data, we identified a single Norwegian isolate belonging to M4NL22, which was sampled after the isolates from this study, possibly suggesting export of M4NL22 to Norway. In conclusion, our study identified a novel S. pyogenes emm4 lineage underlying an increase of iGAS disease in early 2022 in the Netherlands and the results have been promptly communicated to public health officials.

Epidemiological Impact of the Pediatric Live Attenuated Influenza Vaccine (LAIV) Program on Group A Streptococcus (GAS) Infection in England.

Influenza is known to predispose to secondary bacterial infections including invasive group A streptococcal (iGAS) disease. The universal pediatric live attenuated influenza vaccine (LAIV) program introduced in England from the 2013/2014 influenza season was implemented incrementally, introducing cohorts of children annually to 2-16 years of coverage. Additionally, from the beginning of the program, discrete pilot areas offered LAIV vaccination to all primary school-age children, allowing for a unique comparison of infection rates between pilot and nonpilot areas during the program rollout. Cumulative incidence rate ratios (IRRs) of GAS infections (all), scarlet fever (SF), and iGAS infection within each season by age group were compared for pilot and nonpilot areas using Poisson regression. The overall effect of the pilot program in the pre- (2010/2011-2012/2013 seasons) and postintroduction (2013/2014-2016/2017 seasons) periods was assessed using negative binomial regression by comparing changes in incidence between pilot/nonpilot areas (ratio of IRR [rIRR]). Reductions in IRRs of GAS and SF were observed within most post-LAIV program seasons, among the age groups 2-4 and 5-10 years. Significant reductions were seen among 5-10 years (rIRR, 0.57; 95% CI, 0.45-0.71; P < .001), 2-4 years (rIRR, 0.62; 95% CI, 0.43-0.90; P = .011), and 11-16 years (rIRR, 0.63; 95% CI, 0.43-0.90; P = .018) for GAS infections when assessing the overall effect of the program. Our findings suggest that vaccination with LAIV may be associated with a reduced risk of GAS infection and support attaining high uptake of childhood influenza vaccination.

Invasive group A streptococcal disease in Hawke's Bay, New Zealand: epidemiology, manifestations and impact.

To describe the epidemiology, clinical features and healthcare impact of invasive group A streptococcal (iGAS) disease in Hawke's Bay from 2016 to 2021, to inform public health efforts. The case definition of iGAS for this study was isolation of group A streptococcus (GAS) from blood culture. "Severe iGAS" included cases that required intensive care admission or died within 60 days. Cases were identified retrospectively from the Te Whatu Ora Te Matau a Māui Hawke's Bay laboratory database. Clinical data were obtained from inpatient electronic health records. A total of 93 cases of iGAS were identified in Hawke's Bay during the 6-year study period. The overall age-standardised incidence of iGAS was 5.6 per 100,000 (95%CI 4.1-7.4). The incidence was significantly higher among people of Pacific, Māori and Asian ethnicities than European/Other ethnicities, and higher in areas of socio-economic disadvantage. Skin infections were the most common source (70% of cases). Thirty-seven cases (41%) were classified as severe, including 11 deaths (12% case fatality rate). Further action is required to address inequities in social determinants of skin health in Hawke's Bay. Mandatory national notification of iGAS would provide opportunity for improved surveillance of GAS-related disease, and consideration of a public health response to iGAS disease in New Zealand.

Emergency in Group A Streptococcal Infections: Single center data from Turkey.

Emergency in Group A Streptococcal Infections: Single center data from Turkey.

Current scenario of recently rising up cases of invasive group A streptococcal (iGAS) infections in younger children in many European nations: clinical management and prospective counteracting measures – an update

Current scenario of recently rising up cases of invasive group A streptococcal (iGAS) infections in younger children in many European nations: clinical management and prospective counteracting measures – an update

Socio-environmental and clinical features of invasive group A streptococcal disease in the Northern Territory of Australia.

To describe the socio-environmental profile and clinical features of invasive group A streptococcal (iGAS) infections in the Northern Territory (NT) of Australia over 10 years. Cases of iGAS disease diagnosed between 1 May 2011 and 30 April 2021 were retrospectively identified from the NT Notifiable Diseases System and electronic health records accessed. Remoteness of residence, socio-economic index, seasonality and clinical characteristics were recorded. There were 692 cases of iGAS disease identified in the NT during the period 1 May 2011 - 30 April 2021. The age-standardised incidence of iGAS disease was significantly higher in people living in very remote (57.1 cases per 100,000 population, 95% confidence interval [95% CI]: 48.6-65.5) and remote areas (40.9 cases per 100,000 population, 95% CI: 34.7-47.2) than in outer regional areas of the NT (15.7 cases per 100,000 population, 95% CI: 13.4-17.9). People with socio-economic disadvantage were also disproportionately affected, with an incidence of 52.6 cases per 100,000 population (95% CI: 46.2-58.9) in decile 1-3 populations, compared to 8.9 cases per 100,000 population (95% CI: 6.9-10.9) for decile 7-10. For cases with recorded severity data, 135 of 378 (36%) met locally-defined criteria for severe iGAS disease. Recurrent iGAS disease was commonly observed in the dialysis cohort, affecting 17 of the 106 patients during the study period (16% recurrence rate) and causing two deaths. Five molecularly-confirmed clusters of iGAS disease were identified from the study period. iGAS disease is unevenly affecting people in the NT. Those living in areas of socio-economic disadvantage, those in remote and very remote communities, and those receiving dialysis were most affected. It is important that primordial, primary and secondary prevention measures be directed towards supporting these disadvantaged population groups.

Cluster Transmission Drives Invasive Group A Streptococcus Disease Within the United States and Is Focused on Communities Experiencing Disadvantage.

Group A streptococci (GAS), although usually responsible for mild infections, can sometimes spread into normally sterile sites and cause invasive GAS disease (iGAS). Because both the risk of iGAS disease and occurrence of outbreaks are elevated within certain communities, such as those comprising people who inject drugs (PWID) and people experiencing homelessness (PEH), understanding the transmission dynamics of GAS is of major relevance to public health. We used a cluster detection tool to scan genomes of 7552 Streptococcus pyogenes isolates acquired through the population-based Active Bacterial Core surveillance (ABCs) during 2015-2018 to identify genomically related clusters representing previously unidentified iGAS outbreaks. We found that 64.6% of invasive isolates were included within clusters of at least 4 temporally related isolates. Calculating a cluster odds ratio (COR) for each emm type revealed that types vary widely in their propensity to form transmission clusters. By incorporating additional epidemiological metadata for each isolate, we found that emm types with a higher proportion of cases occurring among PEH and PWID were associated with higher CORs. Higher CORs were also correlated with emm types that are less geographically dispersed. Early identification of clusters with implementation of outbreak control measures could result in significant reduction of iGAS.

1158. Pediatric Group A Streptococcal Peritonitis: A Single-Center Eleven Patient Case Series

BackgroundPediatric group A streptococcal peritonitis (GASP) is a rare but serious infection, with few cases reported in the literature. Utah has an unusually high incidence of invasive GAS (iGAS) disease, but the frequency and characteristics of pediatric GASP are unknown.MethodsWe performed a retrospective chart review to identify GASP in Utah children from 2000-2019. GASP was defined as isolation of GAS from peritoneal fluid or blood and clinical signs of peritonitis.Results: Eleven children with GASP were identified, with slight female predominance (n=6). Median age was 6 years; males were significantly younger than females (1.4 versus 7.2 years, p=0.01). GAS was isolated from 4 of 8 blood and 8 of 11 peritoneal cultures obtained. Peritoneal fluid PCR was positive for GAS in one patient. Ten patients underwent laparotomy. Peri-appendiceal inflammation prompted appendectomy in 7 patients; only one had pathologic findings of acute appendicitis. Four patients developed streptococcal toxic shock syndrome and 7 required intensive care. Non-white race (n=4) and lack of appendectomy (n=5) were associated with more severe outcomes. Median antibiotic duration was 27 days. Median hospitalization was 8 days. All patients survived.Figure 1. Schematic representation of GAS peritonitis patient clinical course. Each patient is represented by a single line. Duration of symptoms prior to hospitalization, as well as duration of hospitalization (day 0 representing admission), intensive care, antibiotic administration, and timing of procedural interventions are noted. Duration of antibiotics after discharge for patient 3 was unable to be verified, as indicated by a question mark. Hospitalization, general pediatric hospital care. PICU, pediatric intensive care unit. IR, interventional radiology.ConclusionWe present the largest pediatric case series of GASP to date. Diagnostic hallmarks included gastrointestinal symptoms, fever, systemic inflammation, and peritoneal enhancement without an abdominal source. Peri-appendiceal inflammation was common, although acute appendicitis was rare, and appendectomy was associated with a less severe course. GASP should be considered in patients with acute abdominal processes given increasing incidence of iGAS infections.Disclosures All Authors: No reported disclosures